CD34+ cell responsiveness to stromal cell-derived factor-1alpha underlies rate of engraftment after peripheral blood stem cell transplantation.
BACKGROUND
Stromal cell-derived factor (SDF)-1, a chemokine produced in the bone marrow (BM), is essential for the homing of hematopoietic stem/progenitor cells (HSPCs) to the BM after transplantation. This study examines whether there is a correlation between the in vitro chemotaxis of CD34+ HSPC toward an SDF-1 gradient and in vivo hematopoietic engraftment.


METHODS
Thirty-five patients underwent granulocyte-colony-stimulating factor HSPC collection and autologous transplant with a median dose of 7.7 (range, 3.9-41.5) x 10(6) CD34+ cells per kg body weight. The chemotactic index (CI) of CD34+ cells isolated from leukapheresis products collected from these patients was calculated as the ratio of the percentages of cells migrating toward an SDF-1 gradient to cells migrating to media alone. Expression of the SDF-1 receptor CXCR4 on CD34+ cells was measured by flow cytometry.


RESULTS
Spontaneous cell migration (range, 3.1 +/- 0.6 to 26.5 +/- 7.7%) and SDF-1-directed chemotaxis (11.1 +/- 0.7 to 54.9 +/- 8.3%) of CD34+ cells did not correlate with time to neutrophil engraftment, which occurred at a median of 10 days (range, 8-16 days). Nonparametric tests showed a negative correlation (r = -0.434) between CI and CD34+ cell dose such that neutrophil recovery occurred within the same period in patients transplanted with a lower dose of CD34+ cells but having a high CI as in those transplanted with a higher dose of CD34+ cells but having a low CI. Moreover, CI correlated (r = 0.8) with surface CXCR4 expression on CD34+ cells.


CONCLUSIONS
In patients transplanted with a relatively lower CD34+ cell dose who achieved fast engraftment, a higher responsiveness to SDF-1 and high CI could have compensated for the lower cell dose. However, to apply the CI as a prognostic factor of the rate of engraftment requires validation in a larger number of patients.
Marquez-Curtis
Leah A
LA
Canadian Blood Services, University of Alberta, Edmonton, Alberta, Canada.
Turner
A Robert
AR
Larratt
Loree M
LM
Letcher
Brenda
B
Lee
Siow F
SF
Janowska-Wieczorek
Anna
A
D000328:Adult; D000686:Amyloidosis / Q000378:metabolism / Q000628:therapy; D018952:Antigens, CD34; D001853:Bone Marrow / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000378:metabolism / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects*; D005260:Female; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation; D019718:Receptors, CXCR4 / Q000819:agonists / Q000378:metabolism; D014182:Transplantation, Autologous
D018952:Antigens, CD34; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor